At its early concepts Biohazard 3: Last Escape was going to have a mode where you could play as a zombified Brad Vickers (cut due to production costs) and Jill would have crossed paths with Leon, Ada and William during the story (cut due to continuity problems).

During development, there was another Special Infected called the Screamer, when attacked or agitated, the Screamer would run to a safe location and yell out a loud Scream, calling out a horde of zombies. While it was cut, many things were retained from it. The idea of attracting hordes was given to the Boomer in the form of his Bile. The concept of having to avoid an enemy completely or suffer the consequences was given to the Witch. His scream was given to the Hunter, and his maniacal cackle was given to the Jockey.

The game was originally envisioned by SEGA to be a reboot to the entire franchise, and to build the game similar to the Adventure series, fearing that the previous "Sonic Heroes" and "Shadow the Hedgehog" had made the series stray too far. This also explains the realistic art direction that the game took, along with certain character interactions that don't make sense.

Data exists for a battle situation when the Trainer has no Pokémon, though it isn't actually used when entering a battle with no Pokémon in the final release. In this case, selecting any option other than Run shows the message "Hurry, get away!" This may have been a prototype for the initial battle with the wild Pikachu at the start of the player's adventure, as the player has no Pokémon at that point. It could also have been planned for a possible battle against a wild Spearow with Pikachu unable to battle, making it closer to the events of the anime.

Originally, the Boomers bile was red, and he was meant to have no "puking" capabilities. Instead, he was to explode onto the survivors, dealing significant damage. This was later changed to incorporate the "Screamers" (a cut special infected type) horde-attracting abilities.

In early screenshots and beta art work, Alice had two different necklaces. The first was an A pendant and the other was an upside-down cross. Neither made it to the final version, in which Alice wears her omega necklace.

The game was originally called Conker: Live and Uncut. However, during development the game received heavy censorship. Even minor obscenities which were present in the original N64 version were censored.